This project is designed to determine whether the neonate is at greater risk than the adult from ingestion of potentially toxic heavy metals because of more rapid and/or extensive absorption from the gastrointestinal tract. The absorption kinetics of radiolabelled inorganic salts of lead, cadmium and mercury in the neonate will be compared to those in newly weaned and adult animals. Rats will be used as the primary animal model; important observations made in rats will be tested in a second species, the guinea pig, to provide an indication of the validity of generalizing the findings to man. The absorption of lead, cadmium and mercury will be directly determined using the in vivo segment technique which permits measurement of rates of uptake into the intestinal mucosa, retention in the gut wall and systemic absorption. Where appropriate, the overall extent of absorption of these metals after gastric intubation will be estimated by determination of radioactivity in the carcass after removal of the gastrointestinal tract. Where age-related differences are found, the role of pinocytosis by neonatal gut in the absorption process of these metals will be determined by comparing the absorption kinetics in controls to animals with markedly altered rates of pinocytotic activity resulting from adrenalectomy or glucocorticoid administration. In addition, the significance of binding of these metals to intestinal mucosal cell proteins such as metallothionein will be assessed in attempting to elucidate the mechanism of age-related differences in the absorption kinetics.